tbuckley/cabot-search huggingface dataset:
Development of a quality indicator set to measure and improve quality of ICU care in low- and middle-income countries
Authors: Vrindha Pari, Eva Fleur Sluijs, Maria del Pilar Arias López, David Alexander Thomson, Swagata Tripathy, Sutharshan Vengadasalam, Bharath Kumar Tirupakuzhi Vijayaraghavan, Luigi Pisani, Nicolette de Keizer, Neill K. J. Adhikari, David Pilcher, Rebecca Inglis, Fred Bulamba, Arjen M. Dondorp, Rohit Aravindakshan Kooloth, Jason Phua, Cornelius Sendagire, Wangari Waweru-Siika, Mohd Zulfakar Mazlan, Rashan Haniffa, Jorge I. F. Salluh, Justine Davies, Abigail Beane, Teddy Thaddeus Abonyo, Najwan Abu Al-Saud, Diptesh Aryal, Tim Baker, Fitsum Kifle Belachew, Bruce M. Biccard, Joseph Bonney, Gaston Burghi, Dave A. Dongelmans, N. P. Dullewe, Mohammad Abul Faiz, Mg Ariel Fernandez, Moses siaw-frimpong, Antonio Gallesio, Maryam Shamal Ghalib, Madiha Hashmi, Raphael Kazidule Kayambankadzanja, Arthur Kwizera, Subekshya Luitel, Ramani Moonesinghe, Mohd Basri Mat Nor, Hem Raj Paneru, Dilanthi Priyadarshani, Mohiuddin Shaikh, Nattachai Srisawat, W. M. Ashan Wijekoon, Lam Minh Yen
Journal: Intensive Care Medicine (2022)

To develop a set of actionable quality indicators for critical care suitable for use in low- or middle-income countries (LMICs). A list of 84 candidate indicators compiled from a previous literature review and stakeholder recommendations were categorised into three domains (foundation, process, and quality impact). An expert panel (EP) representing stakeholders from critical care and allied specialties in multiple low-, middle-, and high-income countries was convened. In rounds one and two of the Delphi exercise, the EP appraised (Likert scale 1–5) each indicator for validity, feasibility; in round three sensitivity to change, and reliability were additionally appraised. Potential barriers and facilitators to implementation of the quality indicators were also reported in this round. Median score and interquartile range (IQR) were used to determine consensus; indicators with consensus disagreement (median < 4, IQR ≤ 1) were removed, and indicators with consensus agreement (median ≥ 4, IQR ≤ 1) or no consensus were retained. In round four, indicators were prioritised based on their ability to impact cost of care to the provider and recipient, staff well-being, patient safety, and patient-centred outcomes. Seventy-one experts from 30 countries (n = 45, 63%, representing critical care) selected 57 indicators to assess quality of care in intensive care unit (ICU) in LMICs: 16 foundation, 27 process, and 14 quality impact indicators after round three. Round 4 resulted in 14 prioritised indicators. Fifty-seven respondents reported barriers and facilitators, of which electronic registry-embedded data collection was the biggest perceived facilitator to implementation (n = 54/57, 95%) Concerns over burden of data collection (n = 53/57, 93%) and variations in definition (n = 45/57, 79%) were perceived as the greatest barrier to implementation. This consensus exercise provides a common set of indicators to support benchmarking and quality improvement programs for critical care populations in LMICs.
Association of Tamoxifen and Uterine Sarcoma
Authors: D. Lawrence Wickerham, Bernard Fisher, Norman Wolmark, John Bryant, Joseph Costantino, Leslie Bernstein, Carolyn D. Runowicz
Journal: Journal of Clinical Oncology (2002)

Article Tools SPECIAL DEPARTMENTS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2002.20.11.2758 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 12039943 Association of Tamoxifen and Uterine Sarcoma D. Lawrence WickerhamxD. Lawrence WickerhamSearch for articles by this author , Bernard FisherxBernard FisherSearch for articles by this author , Norman WolmarkxNorman WolmarkSearch for articles by this author , John BryantxJohn BryantSearch for articles by this author , Joseph CostantinoxJoseph CostantinoSearch for articles by this author , Leslie BernsteinxLeslie BernsteinSearch for articles by this author , Carolyn D. RunowiczxCarolyn D. RunowiczSearch for articles by this author Show More NSABP Operations Center, Pittsburgh, PANSABP Biostatistical Center, Pittsburgh, PAUniversity of Southern California School of Medicine, and Norris Comprehensive Cancer Center, Los Angeles, CASt Luke's Roosevelt Hospital Center, New York, NY, This letter was published online ahead of print at www.jco.org. https://doi.org/10.1200/JCO.2002.20.11.2758 First Page Full Text PDF Figures and Tables © 2002 by American Society of Clinical Oncology
Combined alcohol and cannabinoid exposure leads to synergistic toxicity by affecting cerebellar Purkinje cells
Authors: Guichang Zou, Jing Xia, Heyi Luo, Dan Xiao, Jin Jin, Chenjian Miao, Xin Zuo, Qianqian Gao, Zhi Zhang, Tian Xue, Yezi You, Ye Zhang, Li Zhang, Wei Xiong
Journal: Nature Metabolism (2022)
Recombinant <i>Erwinia</i> asparaginase (JZP458) in acute lymphoblastic leukemia: results from the phase 2/3 AALL1931 study
Authors: Luke Maese, Mignon L. Loh, Mi Rim Choi, Tong Lin, Etsuko Aoki, Michelle Zanette, Shirali Agarwal, Robert Iannone, Jeffrey A. Silverman, Lewis B. Silverman, Elizabeth A. Raetz, Rachel E. Rau
Journal: Blood (2022)

AALL1931, a phase 2/3 study conducted in collaboration with the Children's Oncology Group, investigated the efficacy and safety of JZP458 (asparaginase erwinia chrysanthemi [recombinant]-rywn), a recombinant Erwinia asparaginase derived from a novel expression platform, in patients with acute lymphoblastic leukemia/lymphoblastic lymphoma who developed hypersensitivity/silent inactivation to Escherichia coli-derived asparaginases. Each dose of a pegylated E coli-derived asparaginase remaining in patients' treatment plan was substituted by 6 doses of intramuscular (IM) JZP458 on Monday/Wednesday/Friday (MWF). Three regimens were evaluated: cohort 1a, 25 mg/m2 MWF; cohort 1b, 37.5 mg/m2 MWF; and cohort 1c, 25/25/50 mg/m2 MWF. Efficacy was evaluated by the proportion of patients maintaining adequate nadir serum asparaginase activity (NSAA ≥0.1 IU/mL) at 72 hours and at 48 hours during the first treatment course. A total of 167 patients were enrolled: cohort 1a (n = 33), cohort 1b (n = 83), and cohort 1c (n = 51). Mean serum asparaginase activity levels (IU/mL) at 72 hours were cohort 1a, 0.16, cohort 1b, 0.33, and cohort 1c, 0.47, and at 48 hours were 0.45, 0.88, and 0.66, respectively. The proportion of patients achieving NSAA ≥0.1 IU/mL at 72 and 48 hours in cohort 1c was 90% (44/49) and 96% (47/49), respectively. Simulated data from a population pharmacokinetic model matched the observed data well. Grade 3/4 treatment-related adverse events occurred in 86 of 167 (51%) patients; those leading to discontinuation included pancreatitis (6%), allergic reactions (5%), increased alanine aminotransferase (1%), and hyperammonemia (1%). Results demonstrate that IM JZP458 at 25/25/50 mg/m2 MWF is efficacious and has a safety profile consistent with other asparaginases. This trial was registered at www.clinicaltrials.gov as #NCT04145531.
Emergence of genetically linked vaccine-originated poliovirus type 2 in the absence of oral polio vaccine, Jerusalem, April to July 2022
Authors: Neta S Zuckerman, Itay Bar-Or, Danit Sofer, Efrat Bucris, Hagar Morad, Lester M Shulman, Nofar Levi, Leah Weiss, Irina Aguvaev, Zvi Cohen, Klil Kestin, Rinat Vasserman, Michal Elul, Ilana S Fratty, Miranda Geva, Marina Wax, Oran Erster, Ruth Yishai, Lior Hecht-Sagie, Sharon Alroy-Preis, Ella Mendelson, Merav Weil
Journal: Eurosurveillance (2022)

We report an emergence and increase in poliovirus type 2 detection via routine wastewater surveillance in three non-overlapping regions in the Jerusalem region, Israel, between April and July 2022. Sequencing showed genetic linkage among isolates and accumulation of mutations over time, with two isolates defined as vaccine-derived polioviruses (VDPV). This demonstrates the emergence and potential circulation of type 2 VDPV in a high-income country with high vaccine coverage and underscores the importance of routine wastewater surveillance during the polio eradication.
Are involuntary autobiographical memory and déjà vu natural products of memory retrieval?
Authors: Krystian Barzykowski, Chris J. A. Moulin
Journal: Behavioral and Brain Sciences (2022)

Abstract Involuntary autobiographical memories (IAMs) and déjà vu are phenomena that occur spontaneously in daily life. IAMs are recollections of the personal past, whereas déjà vu is defined as an experience in which the person feels familiarity at the same time as knowing that the familiarity is false. We present and discuss the idea that both IAMs and déjà vu can be explained as natural phenomena resulting from memory processing and, importantly, are both based on the same memory retrieval processes. Briefly, we hypothesise that both can be described as “involuntary” or spontaneous cognitions, where IAMs deliver content and déjà vu delivers only the feeling of retrieval. We map out the similarities and differences between the two, making a theoretical and neuroscientific account for their integration into models of memory retrieval and how the autobiographical memory literature can explain these quirks of daily life and unusual but meaningful phenomena. We explain the emergence of the déjà vu phenomenon by relating it to well-known mechanisms of autobiographical memory retrieval, concluding that IAMs and déjà vu lie on a continuum.
Use of Transcarotid Artery Revascularization, Transfemoral Carotid Artery Stenting, and Carotid Endarterectomy in the US From 2015 to 2019
Authors: David P. Stonko, Earl Goldsborough, Pavel Kibrik, George Zhang, Courtenay M. Holscher, Caitlin W. Hicks
Journal: JAMA Network Open (2022)

A transcarotid artery revascularization (TCAR) device was approved by the US Food and Drug Administration in 2015 for carotid revascularization in patients at high risk for stroke, cranial nerve injury, or major cardiac event. It is unclear how the introduction of TCAR has changed the use of carotid endarterectomy (CEA) and transfemoral carotid artery stenting (TFCAS).To quantify the temporal changes in the operative approach to carotid revascularization (CEA vs TFCAS vs TCAR), and to identify patient and disease characteristics commonly associated with each approach.This retrospective cohort study obtained data from the Vascular Quality Initiative database from January 1, 2015, to December 31, 2019. Patients with carotid artery stenosis who underwent CEA, TFCAS, or TCAR were included. Data were analyzed from January to April 2022.Month and year of surgery as well as patient risk status.Number and proportion of carotid revascularization procedures by operative approach.A total of 108 676 patients (mean [SD] age 56.6 [12.5] years; 66 684 men [61.4%]) were included in the analysis. The most common operative approach overall was CEA (n = 81 508 [75.0%]), followed by TFCAS (n = 15 578 [14.3%]) and TCAR (n = 11 590 [10.7%]). The number of procedures increased over the study period (16 754 in 2015 vs 27 269 in 2019; P < .001). In 2015, CEA was used in 84.9% of all cases, followed by TFCAS (14.4%) and TCAR (0.8%). In 2019, CEA was used in 64.8% of cases, followed by TCAR (21.9%) and TFCAS (13.3%). The proportional use of CEA decreased by 5.0% (95% CI, -7.4% to -2.6%) per year, and TCAR use increased by 5.3% (95% CI, 2.3%-8.3%) per year. Among patients at high risk, the change was greater: CEA use decreased by 7.8% (95% CI, -11.9% to -3.8%) per year, TFCAS decreased by 4.8% (95% CI, -9.5% to -0.14%) per year, and TCAR increased by 12.6% (95% CI, 7.1%-18.1%) per year. Multinomial logistic regression showed that patient risk status was the most important characteristic associated with TCAR compared with CEA (relative risk ratio, 36.10; 95% CI, 29.24-44.66; P < .001) and TFCAS (relative risk ratio, 14.10; 95% CI, 11.86-16.66; P < .001). Linear regression revealed no association between year of surgery and in-hospital myocardial infarction, stroke, or mortality.Results of this study indicate that TCAR has become the dominant carotid revascularization approach, surpassing TFCAS and CEA in patients at high risk for stroke, cranial nerve injury, or cardiovascular events. Patient high-risk status was the main characteristic associated with a stenting approach, highlighting the perceived importance of carotid stenting therapies in this patient population.
A digital mask to safeguard patient privacy
Authors: Yahan Yang, Junfeng Lyu, Ruixin Wang, Quan Wen, Lanqin Zhao, Wenben Chen, Shaowei Bi, Jie Meng, Keli Mao, Yu Xiao, Yingying Liang, Danqi Zeng, Zijing Du, Yuxuan Wu, Tingxin Cui, Lixue Liu, Wai Cheng Iao, Xiaoyan Li, Carol Y. Cheung, Jianhua Zhou, Youjin Hu, Lai Wei, Iat Fan Lai, Xinping Yu, Jingchang Chen, Zhonghao Wang, Zhen Mao, Huijing Ye, Wei Xiao, Huasheng Yang, Danping Huang, Xiaoming Lin, Wei-shi Zheng, Ruixuan Wang, Patrick Yu-Wai-Man, Feng Xu, Qionghai Dai, Haotian Lin
Journal: Nature Medicine (2022)

Abstract The storage of facial images in medical records poses privacy risks due to the sensitive nature of the personal biometric information that can be extracted from such images. To minimize these risks, we developed a new technology, called the digital mask (DM), which is based on three-dimensional reconstruction and deep-learning algorithms to irreversibly erase identifiable features, while retaining disease-relevant features needed for diagnosis. In a prospective clinical study to evaluate the technology for diagnosis of ocular conditions, we found very high diagnostic consistency between the use of original and reconstructed facial videos ( κ ≥ 0.845 for strabismus, ptosis and nystagmus, and κ = 0.801 for thyroid-associated orbitopathy) and comparable diagnostic accuracy ( P ≥ 0.131 for all ocular conditions tested) was observed. Identity removal validation using multiple-choice questions showed that compared to image cropping, the DM could much more effectively remove identity attributes from facial images. We further confirmed the ability of the DM to evade recognition systems using artificial intelligence-powered re-identification algorithms. Moreover, use of the DM increased the willingness of patients with ocular conditions to provide their facial images as health information during medical treatment. These results indicate the potential of the DM algorithm to protect the privacy of patients’ facial images in an era of rapid adoption of digital health technologies.
Retraction: CXCR6 Induces Prostate Cancer Progression by the AKT/Mammalian Target of Rapamycin Signaling Pathway
Authors: Jianhua Wang, Yi Lu, Jingchen Wang, Alisa E. Koch, Jian Zhang, Russell S. Taichman
Journal: Cancer Research (2022)

This article (1) has been retracted at the request of the authors. In Fig. 3C, the image depicting endothelial control (EC) was also used in Fig. 4C of a separate 2008 paper by the authors (2). In addition, in Fig. 6A, the α-tubulin bands shown in lanes 3 to 5 for the PC3 cells were also used in lanes 1 to 3 for the C4-2B cells. The authors apologize to the scientific community and deeply regret any inconveniences or challenges resulting from the publication and subsequent retraction of this article.A copy of this Retraction Notice was sent to the last known email addresses for 6 of the 6 authors. Two authors (A.E. Koch, R.S. Taichman) agreed to the retraction; 4 authors did not respond.
Transcriptional and Immune Landscape of Cardiac Sarcoidosis
Authors: Jing Liu, Pan Ma, Lulu Lai, Ana Villanueva, Andrew Koenig, Gregory R. Bean, Dawn E. Bowles, Carolyn Glass, Michael Watson, Kory J. Lavine, Chieh-Yu Lin
Journal: Circulation Research (2022)

Cardiac involvement is an important determinant of mortality among sarcoidosis patients. Although granulomatous inflammation is a hallmark finding in cardiac sarcoidosis, the precise immune cell populations that comprise the granuloma remain unresolved. Furthermore, it is unclear how the cellular and transcriptomic landscape of cardiac sarcoidosis differs from other inflammatory heart diseases.
Quantitative Spatial Profiling of Immune Populations in Pancreatic Ductal Adenocarcinoma Reveals Tumor Microenvironment Heterogeneity and Prognostic Biomarkers
Authors: Haoyang Mi, Shamilene Sivagnanam, Courtney B. Betts, Shannon M. Liudahl, Elizabeth M. Jaffee, Lisa M. Coussens, Aleksander S. Popel
Journal: Cancer Research (2022)

Abstract Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive disease with poor 5-year survival rates, necessitating identification of novel therapeutic targets. Elucidating the biology of the tumor immune microenvironment (TiME) can provide vital insights into mechanisms of tumor progression. In this study, we developed a quantitative image processing platform to analyze sequential multiplexed IHC data from archival PDAC tissue resection specimens. A 27-plex marker panel was employed to simultaneously phenotype cell populations and their functional states, followed by a computational workflow to interrogate the immune contextures of the TiME in search of potential biomarkers. The PDAC TiME reflected a low-immunogenic ecosystem with both high intratumoral and intertumoral heterogeneity. Spatial analysis revealed that the relative distance between IL10+ myelomonocytes, PD-1+ CD4+ T cells, and granzyme B+ CD8+ T cells correlated significantly with survival, from which a spatial proximity signature termed imRS was derived that correlated with PDAC patient survival. Furthermore, spatial enrichment of CD8+ T cells in lymphoid aggregates was also linked to improved survival. Altogether, these findings indicate that thePDAC TiME, generally considered immuno-dormant or immunosuppressive, is a spatially nuanced ecosystem orchestrated by ordered immune hierarchies. This new understanding of spatial complexity may guide novel treatment strategies for PDAC. Significance: Quantitative image analysis of PDAC specimens reveals intertumoral and intratumoral heterogeneity of immune populations and identifies spatial immune architectures that are significantly associated with disease prognosis.
Multi-omic Characterization of Pancreatic Ductal Adenocarcinoma Relates<i>CXCR4</i>mRNA Expression Levels to Potential Clinical Targets
Authors: Florian Kocher, Alberto Puccini, Gerold Untergasser, Agnieszka Martowicz, Kai Zimmer, Andreas Pircher, Yasmine Baca, Joanne Xiu, Johannes Haybaeck, Piotr Tymoszuk, Richard M. Goldberg, Angelica Petrillo, Anthony F. Shields, Mohamed E. Salem, John L. Marshall, Michael Hall, W. Michael Korn, Chadi Nabhan, Francesca Battaglin, Heinz-Josef Lenz, Emil Lou, Su-Pin Choo, Chee-Keong Toh, Silvia Gasteiger, Renate Pichler, Dominik Wolf, Andreas Seeber
Journal: Clinical Cancer Research (2022)

Abstract Purpose: Chemokines are essential for immune cell trafficking and are considered to have a major impact on the composition of the tumor microenvironment. CX-chemokine receptor 4 (CXCR4) is associated with poor differentiation, metastasis, and prognosis in pancreatic ductal adenocarcinoma (PDAC). This study provides a comprehensive molecular portrait of PDAC according to CXCR4 mRNA expression levels. Experimental Design: The Cancer Genome Atlas database was used to explore molecular and immunologic features associated with CXCR4 mRNA expression in PDAC. A large real-word dataset (n = 3,647) served for validation and further exploratory analyses. Single-cell RNA analyses on a publicly available dataset and in-house multiplex immunofluorescence (mIF) experiments were performed to elaborate cellular localization of CXCR4. Results: High CXCR4 mRNA expression (CXCR4high) was associated with increased infiltration of regulatory T cells, CD8+ T cells, and macrophages, and upregulation of several immune-related genes, including immune checkpoint transcripts (e.g., TIGIT, CD274, PDCD1). Analysis of the validation cohort confirmed the CXCR4-dependent immunologic TME composition in PDAC irrespective of microsatellite instability–high/mismatch repair–deficient or tumor mutational burden. Single-cell RNA analysis and mIF revealed that CXCR4 was mainly expressed by macrophages and T-cell subsets. Clinical relevance of our finding is supported by an improved survival of CXCR4high PDAC. Conclusions: High intratumoral CXCR4 mRNA expression is linked to a T cell– and macrophage-rich PDAC phenotype with high expression of inhibitory immune checkpoints. Thus, our findings might serve as a rationale to investigate CXCR4 as a predictive biomarker in patients with PDAC undergoing immune checkpoint inhibition.
Recent advances in dopamine D<sub>2</sub> receptor ligands in the treatment of neuropsychiatric disorders
Authors: Radomir Juza, Kamil Musilek, Eva Mezeiova, Ondrej Soukup, Jan Korabecny
Journal: Medicinal Research Reviews (2022)

Dopamine is a biologically active amine synthesized in the central and peripheral nervous system. This biogenic monoamine acts by activating five types of dopamine receptors (D1-5 Rs), which belong to the G protein-coupled receptor family. Antagonists and partial agonists of D2 Rs are used to treat schizophrenia, Parkinson's disease, depression, and anxiety. The typical pharmacophore with high D2 R affinity comprises four main areas, namely aromatic moiety, cyclic amine, central linker and aromatic/heteroaromatic lipophilic fragment. From the literature reviewed herein, we can conclude that 4-(2,3-dichlorophenyl), 4-(2-methoxyphenyl)-, 4-(benzo[b]thiophen-4-yl)-1-substituted piperazine, and 4-(6-fluorobenzo[d]isoxazol-3-yl)piperidine moieties are critical for high D2 R affinity. Four to six atoms chains are optimal for D2 R affinity with 4-butoxyl as the most pronounced one. The bicyclic aromatic/heteroaromatic systems are most frequently occurring as lipophilic appendages to retain high D2 R affinity. In this review, we provide a thorough overview of the therapeutic potential of D2 R modulators in the treatment of the aforementioned disorders. In addition, this review summarizes current knowledge about these diseases, with a focus on the dopaminergic pathway underlying these pathologies. Major attention is paid to the structure, function, and pharmacology of novel D2 R ligands, which have been developed in the last decade (2010-2021), and belong to the 1,4-disubstituted aromatic cyclic amine group. Due to the abundance of data, allosteric D2 R ligands and D2 R modulators from patents are not discussed in this review.
MEX3A Impairs DNA Mismatch Repair Signaling and Mediates Acquired Temozolomide Resistance in Glioblastoma
Authors: Tian Gan, Yan Wang, Manyi Xie, Qiang Wang, Saisai Zhao, Peng Wang, Qinyu Shi, Xuanchen Qian, Faan Miao, Zhigang Shen, Er Nie
Journal: Cancer Research (2022)

MutS protein homolog 2 (MSH2) is a key element involved in the DNA mismatch repair (MMR) system, which is responsible for recognizing and repairing mispaired bases. Simultaneously, MSH2 identifies DNA adducts induced by temozolomide (TMZ) and triggers apoptosis and autophagy in tumor cells. Previous work has revealed that reduced MSH2 expression is often observed in patients with glioblastoma (GBM) who relapse after chemotherapy. Elucidation of the mechanism behind TMZ-mediated reduction of MSH2 could help improve GBM treatment. Here, we report significant upregulation of Mex-3 RNA binding family member A (MEX3A) in GBM tissues and cell lines following TMZ treatment. MEX3A bound to the MEX3 recognition element (MRE) of MSH2 mRNA, which in turn recruited CCR4-NOT complexes to target MSH2 mRNA for deadenylation and degradation. In addition, ectopic expression of MEX3A significantly decreased cellular DNA MMR activities and reduced the chemosensitivity of GBM cells via downregulation of MSH2, while depletion of MEX3A sensitized GBM cells to TMZ. In MGMT-deficient patients with GBM, MEX3A expression correlated with MSH2 levels, and high MEX3A expression was associated with poor prognosis. Overall, these findings reveal a potential mechanism by which MSH2 expression is reduced in post-TMZ recurrent GBM.A MEX3A/CCR4-NOT/MSH2 axis plays a crucial role in promoting temozolomide resistance, providing new insights into the function of MEX3A and suggesting MEX3A as a potential therapeutic target in therapy-resistant glioblastoma.